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Current status and trends in small nucleic acid drug development:Leading the future

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3802-3817页

作者： yuxi Miao Chen Fu Zhaojin yu Lifeng yu yu Tang Minjie Wei Department of Pharmacology School of PharmacyChina Medical UniversityShenyang 110122China Liaoning Key Laboratory of Molecular Targeted Anti-Tumor Drug Development and Evaluation China Medical UniversityShenyang 110122China Liaoning Medical Diagnosis and Treatment Center Shenyang 110000China Department of Oncology Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang 110042China

Small nucleic acid drugs,composed of nucleotides,represent a novel class of pharmaceuticals that differ significantly from conventional small molecule and antibody-based *** agents function by selectively targeting specific genes or their corresponding messenger RNAs(mRNAs),further modulating gene expression and regulating translation-related *** examples within this category include antisense oligonucleotides(ASO),small interfering RNAs(siRNAs),micro-RNAs(miRNAs),and *** emergence of small nucleic acid drugs as a focal point in contemporary biopharmaceutical research is attributed to their remarkable specificity,facile design,abbreviated development cycles,expansive target spectrum,and prolonged *** challenges such as poor stability,immunogenicity,and permeability issues have been addressed through the integration of chemical modifications and the development of drug delivery *** review provides an overview of the current status and prospective trends in small nucleic acid drug *** with a historical context,we introduce the primary classifications and mechanisms of small nucleic acid ***,we delve into the advantages of the *** and Drug Administration(FDA)approved drugs and mainly discuss the challenges encountered during their *** from researching chemical modification and delivery system that efficiently deliver and enrich small nucleic acid drugs to target tissues,promoting endosomal escape is a critical scientific question and important research direction in siRNA drug *** directions in this field will prioritize addressing these challenges to facilitate the clinical transformation of small nucleic acid drugs.

关键词： Small nucleic acid drugs Oligonucleotide drugs siRNA ASO miRNA Aptamer RNAi Drug development

Mobility and dynamic erosion process of granular flow:insights from numerical investigation using material point method

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Journal of Mountain Science 2024年第8期21卷 2713-2738页

作者： yu Fangwei SU Lijun LI Xinpo ZHAO yu Institute of Mountain Hazards and Environment Chinese Academy of SciencesChengdu 610299China University of Chinese Academy of Sciences Beijing 100049China China-Pakistan Joint Research Center on Earth Sciences Islamabad 45320Pakistan Center for Excellence in Tibetan Plateau Earth Sciences Chinese Academy of SciencesBeijing 100101China College of Civil Engineering and Architecture Zhejiang UniversityHangzhou 310058China MOE Key Laboratory of Soft Soil and Geoenvironmental Engineering Zhejiang UniversityHangzhou 310058China

In order to understand the dynamics of granular flow on an erodible base soil,in this paper,a series of material point method-based granular column collapse tests were conducted to investigate numerically the mobility and dynamic erosion process of granular flow subjected to the complex settings,i.e.,the aspect ratio,granular mass,friction and dilatancy resistance,gravity and presence of water.A set of power scaling laws were proposed to describe the final deposit characteristics of granular flow by the relations of the normalized run-out distance and the normalized final height of granular flow against the aspect ratio,being greatly affected by the complex geological settings,e.g.,granular mass,the friction and dilatancy resistance of granular soil,and presence of water in granular *** index of the coefficient of friction of granular soil was defined as a ratio of the target coefficient of friction over the initial coefficient of friction to quantify the scaling extent of friction change(i.e.,friction strengthening or weakening).There is a characteristic aspect ratio of granular column corresponding to the maximum mobility of granular flow with the minimum index of the apparent coefficient of *** index of the repose coefficient of friction of granular flow decreased gradually with the increase in aspect ratio because higher potential energy of granular column at a larger aspect ratio causes a larger kinetic energy of granular soil to weaken the friction of granular soil as a kind of velocity-related friction *** increase in granular mass reduces gradually the indexes of the apparent and repose coefficients of friction of granular soil to enhance the mobility of granular *** mobility of granular flow increases gradually with the decrease in friction angle or increase in dilatancy angle of granular ***,the increase of gravity accelerates granular flow but showing the same final deposit profile without any dependence on ***

关键词： Column collapse Granular flow Granular soil Material point method Mobility Numerical tests

Single-atom catalysts for neutral zinc-air batteries

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Science China Materials 2024年第5期67卷 1674-1675页

作者： Jiaxu Zhang Minghao yu Faculty of Chemistry and Food Chemistry&Center for Advancing Electronics Dresden(CfAED) Technische Universität DresdenDresden01062Germany

The escalating global energy demand underscores the urgency of developing sustainable battery ***-air batteries(ZABs)have emerged as promising candidates due to their costeffectiveness,safety,and high energy density[1-4].Conventional ZABs typically rely on a four-electron(4e-)oxygen reduction reaction(ORR)in strongly alkaline electrolytes.

关键词： battery neutral typically

Control of Virtual Synchronous Generator for Frequency Regulation Using a Coordinated Self-adaptive Method

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CSEE Journal of Power and Energy Systems 2024年第1期10卷 175-184页

作者： Hongwei Fang Zhiwei yu School of Electrical and Information Engineering and Key Laboratory of Tianjin Electric Power System Simulation and Control Tianjin UniversityTianjin 300072China

Power inverter adopting virtual synchronous generator(VSG)control can provide inertia support for distributed generation ***,it cannot take into account the dynamic regulation characteristics of ***,when the system encounters a sudden change in load or disturbance,the dynamic process of frequency regulation will be greatly *** view of this issue,an improved VSG control strategy based on a coordinated self-adaptive(CSA)method is *** time domain analysis method is used to study the influences of virtual inertia and damping parameter perturbation on the system steady and dynamic ***,in order to make the control strategy suitable for large load changes and suppress frequency variations beyond the limit,the secondary frequency modulation is introduced into the control *** the coordinated adaptive control of virtual inertia,virtual damping and frequency modulation,the dynamic performance of vSG frequency regulation can be obviously *** and experiment results have verified the effectiveness of the proposed CSA control strategy.

关键词： Coordinated self-adaptive method frequency regulation time domain analysis virtual synchronous generator

Effect of relative humidity on the desulfurization performance of calcium-based desulfurizer

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Journal of Environmental Sciences 2024年第4期138卷 179-188页

作者： Juan Lǖ yu Fu Haiyan yu HuanWang Zhe Wang Haiyan Chen School of Environment and Resource Southwest University of Science and TechnologyMianyang 621010China Guangyuan Emergency Management bureau Guangyuan 628000China

Low desulfurization efficiency impedes the wide application of dry desulfurization technology,which is a low-cost and simple process,and one significant solution is the development and manufacture of high-performance *** this study,firstly,a steam jet mill was used to digest quicklime;then,we utilized numerical simulation to study the flow field distribution and analyze the driving factors of quicklime digestion;and lastly,the desulfurization performance of the desulfurizer was evaluated under different relative *** results show that the desulfurizer prepared via the steam jet mill had better apparent activity than traditional ***,the entire jet flow field of the steam jet mill is in a supersonic and highly turbulent flow state,with high crushing intensity and good particle acceleration *** contact with the nascent surface maximizes the formation of slaked *** experiments demonstrated that the operating time with 100%desulfurization efficiency and the“break-through”time for the desulfurizer prepared via the steam jet mill is longer than that of traditional desulfurizers,and has significant advantages,especially at low flue gas relative *** with traditional desulfurizers,the desulfurizer prepared via steam jet mill expands the range of acceptable flue gas temperature,and the failure temperature is 1.625 times that of traditional *** work breaks through the technical bottleneck of low dry desulfurization efficiency,which is an important step in pushing forward the application of dry desulfurization.

关键词： Dry desulfurization Relative humidity Desulfurization efficiency High-efficiency desulfurizer Quicklime digestion

Effectiveness of urban distributed runoff model for discharge and water depth calculation in urban drainage pipe networks

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Journal of Hydrodynamics 2024年第3期36卷 582-591页

作者： Yang Zhou Yi-ling Leng Peng-yu Wang Shang-hong Zhang yu-long Zhu yu-jun Yi School of Water Resources and Hydropower Engineering North China Electric Power UniversityBeijing102206China State Key Laboratory of Water Environment Simulation School of EnvironmentBeijing Normal UniversityBeijing100875China

Effective urban land-use re-planning and the strategic arrangement of drainage pipe networks can significantly enhance urban flood defense *** at reducing the potential risks of urban flooding,this paper presents a straightforward and efficient approach to an urban distributed runoff model(UDRM).The model is developed to quantify the discharge and water depth within urban drainage pipe networks under varying rainfall intensities and land-use *** Nash efficiency coefficient of UDRM exceeds 0.9,which indicates its high computational efficiency and potential benefit in predicting urban *** prediction of drainage conditions under both current and re-planned land-use types is achieved by adopting different flood recurrence *** findings reveal that the re-planned land-use strategies could effectively diminish flood risk upstream of the drainage pipe network across 20-year and 50-year flood recurrence ***,in the case of extreme rainfall events(a 100-year flood recurrence),the re-planned land-use approach fell short of fulfilling the requirements necessary for flood disaster *** these instances,the adoption of larger-diameter drainage pipes becomes an essential requisite to satisfy drainage ***,the proposed UDRM effectively combines land-use information with pipeline data to give practical suggestions for pipeline modification and land-use optimization to combat urban ***,this methodology warrants further promotion in the field of urban re-planning.

关键词： Stormwater runoff water depth urban distributed runoff model urban drainage pipe networks urban land-use re-planning

Equivalent linear model for seismic damage evaluation of single-degree-of-freedom systems representing reinforced concrete structures considering cyclic degradation behavior

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Earthquake Engineering and Engineering Vibration 2024年第3期23卷 637-648页

作者： Lulu Yan Ding-Hao yu Research Center for Geotechnical and Structural Engineering Technology of Liaoning Province Dalian UniversityDalian116622China State Key Laboratory of Coastal and Offshore Engineering Dalian University of TechnologyDalian 116024China

In this study,a novel equivalent damping ratio model that is suitable for reinforced concrete(RC)structures considering cyclic degradation behavior is developed,and a new equivalent linearization analysis method for implementing the proposed equivalent damping ratio model for use in seismic damage evaluation is *** this end,Ibarra’s peak-oriented model,which incorporates an energy-based degradation rule,is selected for representing hysteretic behavior of RC structure,and the optimized equivalent damping for predicting the maximum displacement response is presented by using the empirical method,in which the effect of cyclic degradation is ***,the relationship between the hysteretic energy dissipation of the inelastic system and the elastic strain energy of the equivalent linear system is established so that the proposed equivalent linear system can be directly integrated with the Park-Ang seismic model to implement seismic damage *** to the simplicity of the equivalent linearization method,the proposed method provides an efficient and reliable way of obtaining comprehensive insight into the seismic performance of RC *** verification demonstrates the validity of the proposed method.

关键词： degrading system equivalent linear system equivalent damping seismic damage RC structures

An Enhanced Multiview Transformer for Population Density Estimation Using Cellular Mobility Data in Smart City

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Computers, Materials & Continua 2024年第4期79卷 161-182页

作者： yu Zhou Bosong Lin Siqi Hu Dandan yu College of Computer Science and Software Engineering Shenzhen UniversityShenzhen518060China College of Management Shenzhen UniversityShenzhen518060China Information Center The First Affiliated Hospital of Dalian Medical UniversityDalian116011China

This paper addresses the problem of predicting population density leveraging cellular station *** wireless communication devices are commonly used,cellular station data has become integral for estimating population figures and studying their movement,thereby implying significant contributions to urban ***,existing research grapples with issues pertinent to preprocessing base station data and the modeling of population *** address this,we propose methodologies for preprocessing cellular station data to eliminate any irregular or redundant *** preprocessing reveals a distinct cyclical characteristic and high-frequency variation in population ***,we devise a multi-view enhancement model grounded on the Transformer(MVformer),targeting the improvement of the accuracy of extended time-series population *** experiments,conducted on the above-mentioned population dataset using four alternate Transformer-based models,indicate that our proposedMVformer model enhances prediction accuracy by approximately 30%for both univariate and multivariate time-series prediction *** performance of this model in tasks pertaining to population prediction exhibits commendable results.

关键词： Population density estimation smart city transformer multiview learning

Interactions Between Extracellular Vesicles and Autophagy in Neuroimmune Disorders

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Neuroscience Bulletin 2024年第7期40卷 992-1006页

作者： Xiwen Ai Haojun yu yu Cai Yangtai Guan Department of Neurology Shanghai Jiao Tong University School of Medicine Affiliated Renji HospitalShanghai 200127China Department of Neurology Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794USA

Neuroimmune disorders,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,and Guillain–Barrésyndrome,are characterized by the dysfunction of both the immune system and the nervous *** evidence suggests that extracellular vesicles and autophagy are closely associated with the pathogenesis of these *** this review,we summarize the current understanding of the interactions between extracellular vesicles and autophagy in neuroimmune disorders and discuss their potential diagnostic and therapeutic *** we highlight the need for further research to fully understand the mechanisms underlying these disorders,and to develop new diagnostic and therapeutic strategies.

关键词： Autophagy Extracellular vesicles Neuroimmune disorders Multiple sclerosis Neuromyelitis optica spectrum disorder Myasthenia gravis Guillain-Barré syndrome